ABSTRACT HIV incidence is still increasing in the U.S. despite intense efforts to: (i) diagnose HIV infection as early as possible, (ii) engage newly diagnosed individuals into care and (iii) start antiretroviral therapy (ART) for all infected persons. The San Diego Primary Infection Resource Consortium (PIRC) has been tackling the evolving challenges around these issues for twenty years. The PIRC is the largest, most intensively studied and well-characterized cohort of acute and early HIV infected (AEH) individuals in the United States. It has provided essential support to over 325 peer-reviewed original research manuscripts, spanning a wide range of fields, and including many NIH priority areas for HIV research, including: HIV incidence, strategies to improve HIV testing and entry into prevention services, etc. This application represents a renewal of our PIRC R24 (AI106039) with the proposal to continue this highly productive program, supporting the infrastructure needed to identify, characterize, and share clinical and biological data with scientific colleagues whose research objectives rely upon access to these biological samples and data. The proposed R24 renewal application includes a new collaboration between PIRC and the Center for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) to develop an expanded and synergistic resource to serve biomedical research in the area of AEH. Overall, the PIRC supports: 1) an HIV screening program to detect and stage acute, recent and chronic infection, 2) partner services to identify sexual contacts of newly HIV diagnosed AEH participants (i.e., ?index? subjects), 3) immediate provision of ART, 4) prompt linkage to care, 5) monitoring of ART adherence and continued engagement in care, 6) methods to estimate putative HIV transmission and 6) an AEH biorepository. This entire biorepository and data associated with these well characterized participants are available to qualified investigators, requiring only internal review and approval of a concept proposal. The proposed R24 renewal application will address the following Specific Aims: Aim 1. Community HIV Testing and Acute and Early HIV (AEH) Infection Staging. We propose to identify 120 newly HIV diagnosed persons per year at the University of California San Diego: 47 AEH infected and 73 chronically infected participants. Aim 2. Improve Continuum of HIV Prevention and Treatment. We will evaluate temporal changes in the HIV treatment cascade in response to coordinated efforts to support immediate ART in newly HIV diagnosed PIRC participants. Subjects identified during AEH will be followed for up to 5 years, while chronically infected subjects will be followed in clinic for up to 90 days. Aim 3. Shared Resources. We will leverage AEH specimen and participant resources to support additional NIH research collaborations related to primary HIV infection. Co-enrollment of AEH participants in CNICS will leverage the clinical monitoring of validated outcomes and longitudinal resistance data provided by CNICS. The PIRC will serve as a resource to support high quality basic, clinical and translational research related to AEH.